Q J Med 2003; 96: 369-374
© 2003 Association of Physicians
Relative toxicity of venlafaxine and selective serotonin reuptake inhibitors in overdose compared to tricyclic antidepressants
From the 1 School of Population Health Sciences, Faculty of Medicine and Health Sciences, University of Newcastle, Newcastle, NSW, 2 Department of Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital, NSW, and 3 The Canberra Hospital, Woden, ACT, Australia
Received 27 August 2002 and in revised form 5 February 2003
Background: Selective serotonin reuptake inhibitors (SSRIs) and venlafaxine have been regarded as less toxic in overdose than tricyclic antidepressants (TCAs). Within the TCAs, dothiepin has greater toxicity. Venlafaxine may be more toxic than SSRIs.
Aim: To assess the toxicity in overdose of venlafaxine and SSRIs compared to TCAs, and of dothiepin compared to other TCAs.
Design: Cohort study of prospectively collected data from the Hunter area, NSW, Australia.
Methods: First admissions with antidepressant deliberate self-poisoning (DSP) (November 1994 to April 2000) were identified; the presence of seizures, life-threatening arrhythmias, coma, serotonin toxicity or ICU admission, and QRS duration were noted.
Results: There were 538 admissions, with no deaths. The odds ratio (OR) for seizures with dothiepin vs. other TCAs was 3.4 (95%CI 1.2–9.9). Seizures occurred in 7/51 (14%) venlafaxine overdoses; all patients with seizures consumed 
900 mg. The OR for seizures vs. TCAs was 4.4 (95%CI 1.4–13.8). Coma was less likely with venlafaxine and SSRIs. SSRIs, but not venlafaxine, were less likely to prolong the QRS to 100 ms. ICU admission was less likely for SSRIs. Serotonin toxicity was much more common with venlafaxine and SSRIs.
Discussion: Venlafaxine and dothiepin are pro-convulsant in overdose. Venlafaxine is more likely to cause serotonin toxicity, but less likely to cause coma than TCAs. SSRIs are less likely to cause coma, require ICU admission, or prolong the QRS, but are more likely to cause serotonin toxicity. Antidepressants other than TCAs or venlafaxine should be considered in patients at risk of seizure or suicide.
Address correspondence to Associate Professor I.M. Whyte, Department of Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital, Locked Bag 7, Hunter Region Mail Centre NSW 2310, Australia. e-mail: mdimw{at}cc.newcastle.edu.au
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